Osteoarthritis is characterized by generalized biochemical and water alterations in involved joints; primary or secondary alterations in joint biomechanical forces; differences in levels of catabolins and enzyme activity; sclerosis of subchondral bone; and defined humoral and cell- mediated immunologic abnormalities. These differences from the normal joint may have a major impact on cartilage repair. The specific aims of this proposal are 1) to define whether cartilage repair in osteoarthritic, unstable joints differs quantitatively, qualitatively, or temporally from that seen in normal, stable joints; 2) to assess whether repair of cartilage in stable and unstable joints can be promoted by use of transplants of cultured chondrocytes; and 3) to assess whether repair following abrasion arthroplasty, a commonly used therapeutic clinical modality, differs from that which occurs following well-defined circumscribed full-thickness cartilage defects. Rabbit knees will be studied and osteoarthritis will be experimentally induced by partial meniscectomy. Repair will be evaluated by autoradiographic, histologic, microradiographic, immunohistochemical, quantification of mRNA by Northern analysis, in situ hybridization, and biomechanical methods. The immunogenicity of and the immune response to the cultured chondrocytes will be studied by in vitro techniques. These specific aims are targeted toward an understanding of how and why repair in osteoarthritic joints differs from that in normal joints and have as their long-term goal the development of techniques which will be clinically useful in enhancing repair of osteoarthritic lesions in humans.